Hydrogen bonding potential functions

TABLE 11. Conformational energies (kcalmol1) of ethylenediamine as calculated ab initio (6-31G ), by the original MM3 force field (MM3) and by MM3 augmented with a directional hydrogen bonding potential function (MM 3-94 Reproduced by permission of John Wiley Sons Ltd... 

The hydrogen bond potential function is best illustrated in terms of the resonance structures. 

Idle exponent, m, in the electrostatic attraction term, was taken as unity This value of m is in agreement with, resonance structure II where the two electronegative atoms carry partial charges. The two remaining parameters A and b can be evaluated using Eq. (24) which defines A in terms of b and i 0. The hydrogen bond potential function... 

From the hydrogen bond potential function, Eq. (16), and the first equilibrium condition. Eq. (17), the equation... 

An equation which can be used to evaluate the parameter A in the hydrogen bond potential function is obtained by applying the equilibrium condition given by Eq. (19). 

Equation (24) can also be used to evaluate h by equating values of A in terms of b at different equilibrium X——Y distances and solving for 6. The hydrogen bond potential function, Eq. (16), may be used to calculate the hydrogen bond energy as all the parameters have been evaluated. The hydrogen bond potential function can also be used to obtain the dependence of potential energy on H—X distance and on the X— Y distance. 

R. F. McGuire, F. A. Momany, and H. A. Scheraga, J. Phys. Chem., 76,375 (1972). Energy Parameters in Polypeptides. V. An Empirical Hydrogen Bond Potential Function Based on Molecular Orbital Calculations. 

Box 4.3. An Example of a Hydrogen-Bonding Potential Function Involving Lennard-Jones (A, B), Electrostatic (q) Morse Potentials and Directional Parameters (0). [344]... 

McGuire RF, Momany FA, Scheraga HA (1972) Energy parameters in polypeptides. V. An empirical hydrogen bond potential function based on molecular orbital calculations. J Phys Chem 76 375-393... 

Vedani A, Dunitz JD (1985) Lone-pair directionality in hydrogen bond potential functions for molecular mechanics calculations. The inhibition of human carbonic anhydrase II by sulfonamides. J Am Chem Soc 107 7653-7658... 

Kim, K.H. (1993f). Use of the Hydrogen-Bond Potential Function in Comparative Molecular Field Analysis (CoMFA) An Extension of CoMFA. In Trends in QSAR and Molecular Modelling 92 (Wermuth, C.G., ed.), ESCQM, Leiden (The Netherlands), pp. 245-251. 

Kim, K.H., Greco, G., Novellino, E., Silipo, C. and Vittoria, A. (1993) Use of the hydrogen bond potential function in a comparative molecular field analysis (CoMFA) on a set of benzodiazepines. 

A. Vedani and J. D. Dunitz,/. Am. Chem. Soc., 107, 7653 (1985). Lone-Pair Directionality in Hydrogen Bond Potential Functions for Molecular Mechanics Calculations The Inhibition of Human Carbonic Anhydra.se II by Sulfonamides. 

Following the introdnction of a directional hydrogen bonding potential function into MM3, the parameterization of the force field for the ammonia dimer was undertaken anew . Three conformers were considered, namely 28, 29 and a bifurcated structure 31, and were calcnlated ab initio at the 6-31G level. The results (after corrections for Basis Set Superimposition Error BSSE) favor the linear dimer over the cyclic one by 0.4 kcalmol and yield dimerization energies of —2.49, —2.09 and —0.62 kcalmol for 28, 29 and 31, respectively. A comparison of force field (original MM3 and MM3 with the directional hydrogen bonding function) and ab initio resnlts for the three ammonia... 

Because a typical CoMFA lattice contains at least a thousand grid points, if we want to calculate two types of field for 20 compounds, the total number of interaction energies exceeds 40,000. This large number of calculations is currently feasible only when potential energy functions are used. Typically Lennard-Jones (6-12) steric and Coulombic electrostatic fields, > " and sometimes hydrogen bond potential functions,are used. 

Because lipophilicity is so frequently correlated with potency in traditional QSAR applications, much attention has been paid to this property in CoMFA as well. Hydrophobic interactions are well described by an H2O molecular field computed by means of a combination of steric and hydrogen bond potential functions.9. i7o goth experimental octanol/water log P values and binding data also correlated with log P are well explained. These results are understood by recalling that log P is correlated with a combination of volume or surface area and hydrogen bonding ability. Because these individual properties are accounted by the steric and hydrogen bond or electrostatic potential functions, the hydrophobic effect is also accounted for. 

K. H. Kim, G. Greco, E. Novellino, C. Silipo, and A. Vittoria, /. Comput.-Aided Mol. Design, 7, 263 (1993). Use of the Hydrogen Bond Potential Function in a Comparative Molecular Field Analysis (CoMFA) on a Set of Benzodiazepines. 

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